Objective: To analyze the significance of morphometry and immunohistochemistry in the prognosis of malignant pleural mesothelioma. Methods: Histopathologic material was obtained from 51 decedents who had been diagnosed with pleural tumors in the state of Rio de Janeiro between 1979 and 2000. Pleural tumor biopsies had been routinely fixed in formaldehyde and embedded in paraffin. In 34 of these cases, there was enough material for immunohistochemistry analysis following a slightly modified ABC-method to assay for calretinin, thrombomodulin, CEA, CD15, p53 and Ki-67. The stereological method of "point-sampled intercepts" was used. Results: The most common histopathologic pattern of the mesotheliomas diagnosed was epithelioid (27 cases, 60%). The median survival period for mesotheliomas was 6 months and the 5-year survival rate was 3%. Using Cox proportional hazards model, only 3 variables provided additional prognostic information: female sex (median survival=4 months; p=0.04) and percents of tumor cells staining for thrombomodulin and for p53. Thrombomodulin staining of more than 3.9% mesothelioma cells, and p53 staining of 12% or more, correlated with poor survival (median=3 and 4 months, respectively, p=0.05). For Ki-67, nuclear staining of more than 17.7% of the cells indicated low survival, but the difference was not statistically significant. Conclusions: The identification of thrombomodulin expression and biologic features related to nuclear activity in tumor tissue from patients diagnosed with pleural mesothelioma may have clinical relevance.